NR_163945.1(LDLR-AS1):n.247G>T AND Familial hypercholesterolemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 3, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001929216.3

Allele description [Variation Report for NR_163945.1(LDLR-AS1):n.247G>T]

NR_163945.1(LDLR-AS1):n.247G>T

Genes:

LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]
LDLR-AS1:LDLR antisense RNA 1 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NR_163945.1(LDLR-AS1):n.247G>T

HGVS:

NC_000019.10:g.11089413C>A
NG_009060.1:g.5033C>A
LRG_274:g.5033C>A
NC_000019.9:g.11200089C>A
NR_163945.1:n.247G>T

Links:

dbSNP: rs879254374

NCBI 1000 Genomes Browser:

rs879254374

Molecular consequence:

NR_163945.1:n.247G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Familial hypercholesterolemia (FH)
Identifiers:: MONDO: MONDO:0005439; MedGen: C0020445; OMIM: PS143890

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002198380	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 3, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 7937987, 8664911, 15359125, 16250003, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002198380

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 3, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A single-base substitution in the proximal Sp1 site of the human low density lipoprotein receptor promoter as a cause of heterozygous familial hypercholesterolemia.

Koivisto UM, Palvimo JJ, Jänne OA, Kontula K.

Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10526-30.

PubMed [citation]

PMID:: 7937987
PMCID:: PMC45054

An LDL receptor promoter mutation in a heterozygous FH patient with dramatically skewed ratio between the two allelic mRNA variants.

Jensen LG, Jensen HK, Nissen H, Kristiansen K, Faergeman O, Bolund L, Gregersen N.

Hum Mutat. 1996;7(1):82-4. No abstract available.

PubMed [citation]

PMID:: 8664911

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002198380.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant disrupts the c.-136C nucleotide in the LDLR gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 7937987, 8664911, 15359125, 16250003). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1426080). This variant has been observed in individual(s) with clinical features of autosomal dominant familial hypercholesterolemia (Invitae). This variant is not present in population databases (gnomAD no frequency). This variant occurs in a non-coding region of the LDLR gene. It does not change the encoded amino acid sequence of the LDLR protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 14, 2024

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